Efficacy of methotrexate as anti‑inflammatory and anti‑proliferative drug in dermatology: Three case reports

Nedelcu,Roxana‑Ioana; Balaban,Mihaela; Turcu,Gabriela; Brinzea,Alice; Ion,Daniela   Adriana; Antohe,Mihaela; Hodorogea,Anastasia; Calinescu,Andreea; Badarau,Anca   Ioana; Popp,Cristiana   Gabriela; Cioplea,Mirela; Nichita,Luciana; Popescu,Silvia; Diaconu,Carmen; Bleotu,Coralia; Pirici,Daniel; Popescu,Raluca; Popescu,Catalin   Mihai; Zurac,Sabina   Andrada

doi:10.3892/etm.2019.7511

Efficacy of methotrexate as anti‑inflammatory and anti‑proliferative drug in dermatology: Three case reports

Authors:
- Roxana‑Ioana Nedelcu
- Mihaela Balaban
- Gabriela Turcu
- Alice Brinzea
- Daniela Adriana Ion
- Mihaela Antohe
- Anastasia Hodorogea
- Andreea Calinescu
- Anca Ioana Badarau
- Cristiana Gabriela Popp
- Mirela Cioplea
- Luciana Nichita
- Silvia Popescu
- Carmen Diaconu
- Coralia Bleotu
- Daniel Pirici
- Raluca Popescu
- Catalin Mihai Popescu
- Sabina Andrada Zurac
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Affiliations: Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 050474 Bucharest, Romania, Department of Dermatology, Colentina Clinical Hospital, 020125 Bucharest, Romania, Department of Cellular and Molecular Pathology, ‘Stefan S. Nicolau’ Institute of Virology, 030304 Bucharest, Romania , Department of Pathology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
Published online on: April 19, 2019 https://doi.org/10.3892/etm.2019.7511
Pages: 905-910

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Abstract

Methotrexate (MTX) is a folic acid analog with anti‑proliferative (anti‑neoplastic, cytotoxic), immunosuppressive and anti‑inflammatory properties, which has been used in the treatment of various cutaneous disorders, such as psoriasis, keratoacanthoma, pityriasis rubra pilaris, atopic dermatitis, mycosis fungoides, bullous skin diseases, systemic sclerosis, morphea, lupus erythematosus, dermatomyositis and crusted scabies. Inhibition of cell proliferation is explained through its role in blocking DNA/RNA synthesis, by inhibiting dihydrofolate reductase, necessary for the production of pyrimidine and purine nucleotides. An anticancer effect can be related to α‑oxoaldehyde metabolism (MTX increases methylglyoxal levels). Its anti‑inflammatory property is based on the inhibition of 5‑aminoimidazole‑4‑carboxamide ribonucleotide transformylase, thus increasing intracellular and extracellular adenosine, a purine nucleoside with anti‑inflammatory effect. This drug can limit inflammation by scavenging free radicals and decreasing malondialdehyde‑acetaldehyde protein‑adduct production. Moreover, the anti‑proliferative and anti‑inflammatory effects can also be related to inhibition of the DNA methylation pathway, thus inhibiting methionine formation. The aim of the present study was to report various dermatological cases from our daily practice that demonstrate the efficacy of MTX in the treatment of cutaneous diseases, highlighting different mechanisms of action: its anti‑inflammatory effect in psoriasis and its anti‑proliferative, and anti‑neoplastic effect in well‑differentiated squamous cell carcinoma or in keratoacanthoma. Moreover, different administration pathways and doses are addressed. Assessment of the treatment plan, clinical improvement of cutaneous lesions, biologic evaluation, final aesthetic result, quality of life, as well as potential adverse effects and drug tolerance related to each case mentioned.

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